I. Field of the invention
This invention relates to a medical device used to reduce tissue injury resulting from ischemia, occurring naturally, through trauma or from surgery.
II. Description of Related Art
Tissue in the human body is regulated at a constant temperature of approximately 37 C. An essential part of this regulation is achieved by adequate perfusion of body fluids. Blood perfusion carries out many functions in addition to heat exchange, namely oxygenation of tissue. Without blood perfusion and therefore oxygen delivery, tissue becomes ischemic. For example, normal flow to the brain ranges from 46 to 62 ml/min per 100 grams of brain matter. An accepted critical ischemic threshold is 20 ml/min per 100 grams of brain matter [Reference Cardiovascular Physiology, W. Milnor, pg. 395, 1990]. Unfortunately this threshold is reached during acute ischemic injury, such as stroke, heart attack, or spinal injury. Ischemic thresholds also take place during the course of an initial injury, such as brain swelling after trauma, or reperfusion of occluded coronary/cerebral arteries.
In addition to steps taken to rapidly restore blood perfusion levels above ischemic thresholds, research shows induced hypothermia holds promise for protecting organ tissue from ischemic injury. Among other mechanisms, hypothermia decreases tissue metabolism, concentrations of toxic metabolic byproducts, and suppresses the inflammatory response in the aftermath of ischemic tissue injury. Depending on the time of initiation, hypothermia can be intra-ischemic, post-ischemic, or both. Hypothermic ischemic protection is preventive if tissue metabolism can be closed down. Hypothermia may also enhance recovery by ameliorating secondary tissue injury or decreasing ischemic edema formation. Since the metabolic reduction is less than 10% per degree Celsius, only deep hypothermia, targeting 20–25 degrees Celsius, conceivably provides adequate tissue protection via metabolic slowdown. Secondary tissue injury, thought to be mainly caused by enzymatic activity, is greatly diminished by mild to moderate hypothermia targeting 32–35 degrees Centigrade. As early as 24 hours after onset of ischemia, secondary tissue injury can set off a mass effect with damaging effects on viable surrounding tissues. Late post-ischemic hypothermia decreases edema formation, protecting tissue at risk.
With this in mind, physicians have tried to harness the benefits of hypothermia using a variety of cooling techniques. These techniques vary depending on clinical circumstances. For example, in preventive cooling the goal may be locally applied deep hypothermia, whereas in acute ischemic syndromes, systemic mild to moderate hypothermia may be preferred. The primary focus to this point has been systemic body surface or vascular cooling, only a few concepts have embarked on local, organ specific or cerebrospinal fluid cooling. Systemic cooling has specific limitations and drawbacks related to its inherent unselective nature. For example, research has shown that systemic or whole body cooling may lead to cardiovascular irregularities like reduced cardiac output and ventricular fibrillation, an increased risk of infection, and blood chemistry alterations. Local cooling approaches have been limited by the technological challenges related to developing tiny heat exchangers for small arterial vessels. These vessel inner diameters are 6 mm or smaller.
As a result, the challenge of organ specific cooling is the development of heat exchange catheters that meet the cooling requirements without causing significant physiological disruption. Fortunately, heat exchanger design is not a new science and numerous enhancement techniques have been employed for decades to performance. Two obvious examples include the condenser coil of your home air conditioning system and the radiator of your car. Regardless of the enhancement technique, each approach attempts to achieve one or a combination of the following objectives: 1) reduce the size of the heat exchange device, 2) increase the UA (U, the overall transport coefficient and A, the exchange surface area) to increase the heat exchange rate or reduce the required temperature differences used to drive the exchange process, and 3) reduce the pumping power required to meet a heat exchange target value. (Reference: Principles of Enhanced Heat Transfer, R. Webb, pg. 2, 1994).
For the cooling catheters used to cool organs and not the entire body, the objective is clear: reduce the size of the heat exchange catheter so that in can be placed safely inside an artery while maintaining a adequate heat transfer rate. To understand the design process, consider the following idea. An analogy can be made between electrical behavior and heat transfer; that is the total heat exchange, Q, is proportional to the ratio of the temperature difference (delta T) to the total sum of the heat transfer resistances (Rtotal), Q=(delta T/Rtotal). This is similar to Ohm's law where the current, I, is proportional to the ratio of the voltage difference to the sum of the electrical resistances.
To select the correct heat transfer enhancement approach for cooling catheters requires balancing two goals: (1) the goal to maximize heat transfer rates to enable sufficient device size reductions and (2) the goal to minimize fluid pressure drop increases to sustain safe organ blood perfusion levels.
Consider the first goal: heat transfer augmentation to minimize size. The first step is to determine the dominant heat transfer resistance and reducing it as much as possible. FIG. 1 shows how the overall heat transfer rate can be affected by changes in heat transfer resistances when we assume a reasonable cooling catheter heat transfer resistance breakdown: 70% of the total resistance comes for the blood-side convective heat transfer resistance, 18% for the coolant-side convective resistance, and 12% from the conductive heat transfer resistance. Looking at the impact of coolant-side resistance (the solid line) on the heat transfer rate ratio (the y-axis), in FIG. 1, we can see that reducing the coolant-side resistance does not provide substantial heat transfer augmentation. To significantly boost cooling catheter performance, the focus should blood side resistance reduction (the dashed line in FIG. 1).
Now consider the second cooling catheter design goal: minimizing pressure drop. Despite the reviewed specifications described for existing cooling catheter patents, heat transfer enhancement is only part of the cooling catheter design challenge. For example if a catheter designer attempts to minimize the dominant heat transfer resistance one may add surface area or rough surfaces to produce turbulent mixing near the heat transfer surface. These attempts likely will boost the heat transfer performance significantly, but they will also likely reduce perfusion rates because of an increased pressure drop levels across the enhanced surfaces. FIG. 2 shows an example of a cylindrical cooling catheter design. In this example the ratio of the cooling catheter radius to the vessel radius is shown as Ri/Ro. If we assume that the heart is analogous to a single speed pump, as the ratio of radii increases the pressure drop across the catheter increases, until the heart cannot overcome this hydraulic resistance and perfusion rates fall. At that point the flow past the cooling device decreases and the heat transfer performance also rapidly falls. This example demonstrates that a single-minded attempt to increase heat transfer rates can reduce organ perfusion levels.
Heat transfer enhancement techniques can be broken down into two broad categories: (1) passive techniques and (2) active techniques. Related endovascular cooling catheter patents to this point have relied solely on passive transport enhancement techniques, where a fixed or static cooling catheter is placed inside a stagnant or moving body fluid. FIG. 2A shows a passively enhanced cooling catheter inside a blood vessel (U.S. Pat. No. 6,096,068, Dobak et al. 2000). Unlike most active enhancement techniques, the heat exchange surfaces for these passive enhancement techniques remain motionless during the heat transfer process.
Consequently, passive techniques are transport enhancement approaches that do not add mixing energy to the fluid system of interest. The energy used to create enhanced performance is taken from or drawn from the stored hydraulic energy involved in the exchange process. They are particularly effective when fluid pumping power or hydraulic energy is not limited or prohibitive in cost. The approach involves adding surface area and or inducing turbulence adjacent to the effective exchange surface area (FIG. 2A). These approaches are also used throughout the heating and air conditioning industry where fluid pumping power or hydraulic energy can easily be increased. This differs, however, from the human body where physiological constraints naturally limit the hydraulic energy or fluid pumping power. In turn, aggressive passive enhancement techniques, particularly in small vessels, like those that lead to individual organs like the brain, spinal cord, or kidney, are likely to lead to substantial blood side pressure drops that may affect cardiac output and or organ perfusion.
U.S. Pat. No. 6,096,068, by Dobak and Lasheras (Aug. 1, 2000) describes a metallic cooling catheter used to exchange heat inside the body. To enhance heat transfer, articulated segments are used to increase surface area and induce turbulence, a classic passive enhancement technique. Clock-wise and counter clock-wise segments mix the thermal boundary layer in highly pulsatile flow inside the carotid artery, creating a turbulence intensity, I, of greater than 0.05 (1 equals the RMS velocity fluctuation/mean velocity). This patent, however, does not address the critical issue of device blood-side pressure drop, the inherent cost resulting from a heat transfer enhancement technique. In fact the turbulence generated with devices like these does not come without some fluid energy cost (FIG. 2A). In this case, fluid energy is lost through shear stresses in the fluid, also called viscous dissipation, where kinetic energy is irreversibly converted to thermal energy or molecular motion. The end result is increased pressure drop. So while the aggressive clockwise and counter-clockwise segments may be effective in large inner diameter vessel like the vena cava, used for systemic cooling, aggressive passive enhancement techniques if used in the smaller vessels, like the common carotid, are likely to lead to brain perfusion reductions that can worsen the ischemic injury to the brain. Furthermore, aggressive techniques like these when in contact with the vascular wall may disrupt unstable plaque and generate emboli and create further ischemic injury, especially if there is not a method to avoid catheter surface to vessel wall contact. Consequently, turbulence intensity alone is not a sufficient indicator of an effective endovascular heat exchanger for small arteries.
There are two more concerns with this patent (U.S. Pat. No. 6,096,068, Dobak and Lasheras (Aug. 1, 2000)): a) the coolant side pressure drop is large, equal to five atmospheres or 3800 mmHg; a catheter fracture failure would lead to a high pressure liquid jet impinging upon the vascular wall and b) the articulated segments are prone to thrombus generation due to blood flow stagnation zones that will inherently be established along the catheter surface.
Two other patents by Gobin et al., U.S. Pat. No. 6,126,684 (Oct. 3, 2000) and Dae, U.S. Pat. No. 6,231,594 (May 5, 2001) address endovascular cooling with inflatable static balloons. By static balloons we mean the balloon walls that remain motionless once they are inflated and the heat exchange process has begun. This approach is useful for device insertion and for increased exchange surface area when the cooling action is begun. Gobin et al. uses multiple balloon chambers with a coolant distribution technique to ensure a maximum temperature difference between coolant and blood flow. The multiple chambers help maintain catheter flexibility. The Dae patent, similar to Gobin et al., uses multiple balloons twisted into a helix with separate cooling pathways. In both of these designs heat exchange effectiveness is driven by two factors: 1) the increased heat exchange surface area (a passive enhancement approach) and 2) the carefully circulated coolant pathways. This is in contrast with the Dobak and Lasheras patent (U.S. Pat. No. 6,096,068 Aug. 1, 2000) discussed above that relied primarily on turbulence intensity boosts for improved heat transfer. Furthermore, in both of these balloon catheter patents information is not provided on the impact of device inflation on normal blood flow nor is there information provided on the internal coolant pressure. In addition, both patents do not address the issue of blood hemodynamics leading to flow stagnation zones on the catheter that are likely sites for thrombus generation.
In yet another patent by Keller et al., U.S. Pat. No. 6,264,679 (Jul. 24, 2001) a third approach is taken for endovascular cooling. Using small hollow fibers, coolant is passed from one manifold to the next. The arrangement is similar to a tube and shell heat exchanger used throughout large cooling systems such as chillers. This approach attempts to maximize the available heat exchange surface area and maintain a well-distributed coolant to ensure the maximum temperature difference between the coolant and the blood. This patent also does not address the fundamental design challenge of avoiding increased fluid pressure drops nor does it address the concern of blood stagnation zones inside the hollow fiber bundle.
In summary these endovascular cooling techniques mentioned above have one or more of these disadvantages.                a) In general, these designs have low heat exchange surface area to device volume ratios. This leads to deleterious vessel occlusion characteristics, particularly with smaller arterial blood vessels, increasing the chance for further ischemic injury.        b) The designs are likely to have blood flow stagnation zones, likely sites for thrombus formations. There are many crevices within each design that are not washed effectively.        c) In general, these designs have high internal coolant pressures because the working fluids must be circulated at high rates through small passageways to maintain high heat transfer effectiveness. In fact, in some cases this internal pressure is as high as 3800 mmHg gauge pressure, making device rupture a potentially harmful failure mode.        d) The designs do not state a method to maintain the exchange catheter orientation inside the center of a blood vessel to avoid emboli generation and to maintain maximum exchange performance. This is a particularly important problem when the device size is nearly equal to the blood vessel.        e) These designs do not offer the ability to transfer therapeutic drugs or physiological gases as needed simultaneously with the heat transfer process. They do not explore the idea of using porous materials to transfer heat and mass.        
While endovascular heat exchangers have not employed active mixing to augment transport, some other applications are noted. Reeder et al. U.S. Pat. No. 6,217,826 (Apr. 17, 2001) and Borovetz et al. U.S. Pat. No. 6,348,175 (Feb. 19, 2002) each describe the value of active mixing enhancement for a blood pump design. Furthermore, Hattler et al. U.S. Pat. No. 5,501,663 (Mar. 26, 1996), describes an endovascular mass exchanger that uses active mixing. It uses a balloon with porous fibers to enhance mass transfer between a low viscosity blood gas flowing within the fibers and the blood flow surrounding the fibers. Krantz et al. U.S. Pat. No. 5,626,759 (May 6, 1997) also uses active mixing for blood oxygenation outside the body. In this patent, blood flows inside hollow fibers that are vibrated in an axial direction held inside a bedside container.